1. Field of the Invention
The present invention relates to Magnetic Resonance Imaging-Guided (MRI-Guided) medical procedures, particularly MRI-Guided interventional procedures and therapies that are performed on the breasts or mammaries of patients.
2. Background of the Art
The diagnosis and treatment of breast cancer is a major health care issue which affects the lives of more than 180,000 women annually, only considering the United States. While, early detection and treatment of breast cancer is a major factor for efficient patient management, there is significant technical space available for developing a highly efficient approach for diagnosing and characterizing breast cancer. Although numerous studies manifest an almost 100% sensitivity of MRI for the detection of breast cancer, the studies also demonstrate a widely varying specificity. These findings result in a patient management dilemma when lesions are detected with MRI and those lesions have not been seen with other gold standard modalities. MRI-Guided biopsy or MRI-Guided wire localization therefore will be important in integrating MRI into breast cancer management. Furthermore, it is reasonable to suggest that the combination of MRI diagnostic imaging, for example contrast agent perfusion, with MRI guided subcutaneous core biopsy may provide an improved method for the detection and characterization of breast cancer. In addition, breast conserving therapies (BCT), such as laser photo-ablation therapy, are under evaluation. These approaches require accurate positioning and monitoring of their effect (e.g. tissue temperature) during insertion and during the actual procedure. Visualization can be achieved in real-time with MRI systems. Thus an apparatus to position interventional devices and monitor their operation under MRI guidance would be likely to improve the success of diagnostic and therapeutic procedures.
Several MR-guided free-hand or stereotaxic apparatus have been implemented for interventions of the breast, such as preoperative localization, fine needle aspiration biopsy and core biopsy (U. Fischer, et al., “MR Imaging-Guided Biopsy Breast Intervention: Experience with Two Systems” Radiology 192, 876-881, (1994); U. Fischer, et al., “MR-Guided Biopsy of Suspected Breast lesions with a Simple Stereotaxic Add-On Device for Surface Coils” Radiology 200, 651-658 (1996)), (C. K. Cuhl, et al., “Interventional Breast MR Imaging: Clinical Use of a Stereotaxic Localization and Biopsy Device” Radiology 204, 667-675 (1997); S. H. Heywang-Kobrunmner, et al., “Prototype Breast Coil for MR-Guided needle Localization” J. Comp. Assist. Tomogr. 18, 876-881 (1994)) and (S. Greenstein-Orel, et al., “MR Imaging-Guided Localization and Biopsy of Breast Lesions: initial Experience” Radiology, 193, 97-102 (1994); E. K. Insko, et al., “Multicoil Array for High Resolution Imaging of the Breast” Magn. Reson. Med. 37, 778-784 (1997)). The design and the operation of these devices are tailored for use inside the limited space of an MRI scanner, and a short contrast window (5 to 10 min). Such studies have demonstrated the feasibility of combining MRI, as a diagnostic modality, with MR-guided interventions of the breast. The common features of such devices are: (a) compression of the breast for better fixation, with one or two plates and (b) use of an arrangement of puncture channel (mesh) to correctly place the interventional probe. Despite their success, there are some limitations in these designs, particularly when they are compared with the non-MR stereotaxic devices. First, most of the devices provide compression along a specific orientation, usually medial-lateral, which may not be the optimal one, as for example for transversing the shortest path in the tissue or to reach areas such as the axilla. Second, in most of the devices the probe is directed by means of a mesh, and thus it can be only inserted perpendicular to the compression plates or with a slight “free-hand” angulation. This may not be the optimal approach, for example, when attempting to access tissue close to the chest wall, at the axilla or to avoid obstructions such as implants. The two single plate systems have the same limitations and in addition there is the potential for accidental rib puncture or highly invasive operations behind the nipples. The operation of the above devices requires the patient to be removed from the magnet, the probe inserted and then re-imaged, with the possibility that another insertion may be required to correct the initial one. This practice increases the length of the operation, and may not be always feasible due to the limited number of allowed injections of contrast material and the short duration of the contrast window.
Several types of interventional devices, including such devices as catheters, ultrasonic devices, transcanular devices, excavating tools, therapeutic tools (e.g., lasers, cryoablation, drug delivery, electrical stimulating devices, etc.) have been used in MRI-Guided procedures in the breast including within them MRI compatible features such as such as non-specific surface RF coils (U. Fischer, et al., “MR Imaging-Guided Biopsy Breast Intervention: Experience with Two Systems” Radiology 192, 876-881, (1994); U. Fischer, et al., “MR-Guided Biopsy of Suspected Breast lesions with a Simple Stereotaxic Add-On Device for Surface Coils” Radiology 200, 651-658 (1996)), modified RF coils (C. K. Cuhl, et al., “Interventional Breast MR Imaging: Clinical Use of a Stereotaxic Localization and Biopsy Device” Radiology 204, 667-675 (1997); S. H. Heywang-Kobrunner, et al., “Prototype Breast Coil for MR-Guided needle Localization” J. Comp. Assist. Tomogr. 18, 876-881 (1994)) and a multi-coil array (S. Greenstein-Orel, et al., “MR Imaging-Guided Localization and Biopsy of Breast Lesions: initial Experience” Radiology, 193, 97-102 (1994); E. K. Insko, et al., “Multicoil Array for High Resolution Imaging of the Breast” Magn. Reson. Med. 37, 778-784 (1997)). These RF coils, except for those shown in Greenstein-Orel, et al. and E. K. Insko, et al., are of standard dimensions and are not appropriate for use with the proposed apparatus since they will have a variable filling-factor for different degrees of breast compression. To address these issues, and others analyzed herein, different methodologies are needed in the field.
While endoscopic, arthroscopic, and endovascular therapies have already produced significant advances in health care, these techniques ultimately suffer from the same limitation. This limitation is that the accuracy of the procedure is “surface limited” by what the surgeon can either see through the device itself or otherwise visualize (as by optical fibers) during the course of the procedure. That is, the visually observable field of operation is quite small and limited to those surfaces (especially external surfaces of biological masses such as organs and other tissue) observable by visible radiation, due to the optical limitations of the viewing mechanism. MR imaging, by comparison, overcomes this limitation by enabling the physician or surgeon to non-invasively visualize tissue planes and structures (either in these planes or passing through them) beyond the surface of the tissue under direct evaluation. Moreover, MR imaging enables differentiation of normal from abnormal tissues, and it can display critical structures such as blood vessels in three dimensions. Prototype high-speed MR imagers which permit continuous real-time visualization of tissues during surgical and endovascular procedures have already been developed. MR-guided minimally invasive therapy is expected to substantially lower patient morbidity because of reduced post-procedure complications and pain. The use of this type of procedure will translate into shorter hospital stays, a reduced convalescence period before return to normal activities, and a generally higher quality of life for patients. The medical benefits and health care cost savings are likely to be very substantial.
New technologies like intra-operative magnetic resonance imaging and nonlinear magnetic stereotaxis, the latter discussed by G. T. Gillies, R. C. Ritter, W. C. Broaddus, M. S. Grady, M. A. Howard III, and R. G. McNeil, “Magnetic Manipulation Instrumentation for Medical Physics Research,” Review of Scientific Instruments, Vol. 65, No.3, pp.533-562 (March 1994), as two examples, will likely play increasingly important roles here. In the former case, one type of MR unit is arranged in a “double-donut” configuration, in which the imaging coil is split axially into two components. Imaging studies of the patient are performed with this system while the surgeon is present in the axial gap and carrying out procedures on the patient. A second type of high-speed MR imaging system combines high-resolution MR imaging with conventional X-ray fluoroscopy and digital subtraction angiography (DSA) capability in a single hybrid unit. These new generations of MR scanners are able to provide the clinician with frequently updated images of the anatomical structures of interest, therefore making it possible to tailor a given interventional procedure to sudden or acute changes in either the anatomical or physiological properties of, e.g., a part of the brain into which a drug agent is being infused.
Nonlinear magnetic stereotaxis is the image-based magnetically guided movement of a small object directly through the bulk brain tissues or along tracts within the neurovasculature or elsewhere within the body. Electromagnets are used to magnetically steer the implant, giving (for example) the neurosurgeon or interventional neuroradiologist the ability to guide the object along a particular path of interest. (The implant might be either magnetically and/or mechanically advanced towards its target, but is magnetically steered, in either case. That is, magnetic fields and gradients are used to provide torques and linear forces to orient or shift the position of the implant or device, with a mechanical pushing force subsequently providing none, some, or all of the force that actually propels the implant or device. Additional force may be provided magnetically.) The implant's position is monitored by bi-planar fluoroscopy, and its location is indicated on a computerized atlas of brain images derived from a pre-operative MR scan. Among other applications, the implant might be used to tow a pliable catheter or other drug delivery device to a selected intracranial location through the brain parenchyma or via the neurovasculature. Magnetic manipulation of catheters and other probes is well documented in research literature. For example, Cares et al. (J. Neurosurg, 38:145, 1973) have described a magnetically guided microballoon released by RF induction heating, which was used to occlude experimental intracranial aneurysms. More recently, Kusunoki et al. (Neuroradiol 24: 127, 1982) described a magnetically controlled catheter with cranial balloon useful in treating experimental canine aneurysms. Ram and Meyer (Cathet. Cardiovas. Diag. 22:317, 1991) have described a permanent magnet-tipped polyurethane angiography catheter useful in cardiac interventions, in particular intraventricular catheterization in neonates.
U.S. Pat. No. 4,869,247 teaches the general method of intra parenchymal and other types of magnetic manipulation, and U.S. Pat. Nos. 5,125,888; 5,707,335; and 5,779,694 describe the use of nonlinear magnetic stereotaxis to maneuver a drug or other therapy delivery catheter system within the brain. U.S. Pat. No. 5,654,864 teaches a general method of controlling the operation of the multiple coils of a magnetic stereotaxis system for the purpose of maneuvering an implant to precisely specified locations within the body. Both of these technologies offer a capability for performing image-guided placement of a catheter or other drug delivery device, thus allowing drug delivery directly into the brain via infusion through the walls of the catheter or out flow of the tip off the catheter. In the case of drug delivery directly into the brain tissues, the screening of large molecular weight substances by the endothelial blood-brain barrier can be overcome. In the case of infusions into specific parts of the cerebrovasculature, highly selective catheterizations can be enabled by these techniques. In either case, however, detailed visual images denoting the actual position of the drug delivery device within the brain would be extremely useful to the clinician in maximizing the safety and efficacy of the procedure. The availability of an MR-visible drug delivery device combined with MR-visible drug agents would make it possible to obtain near real-time information on drug delivery during interventional procedures guided by non-linear magnetic stereotaxis. Drug delivery devices, such as catheters, that are both MR-visible and radio-opaque could be monitored by two modalities of imaging, thus making intra-operative verification of catheter location possible during nonlinear magnetic stereotaxis procedures. (Intra-operative MR assessment might require the temporary removal of the magnetic tip of the drug delivery catheter and interruption of the magnetic stereotaxis procedure to image the patient.).
In the treatment of all diseases, and especially neurological diseases and disorders, targeted drug delivery can significantly improve therapeutic efficacy, while minimizing systemic side-effects of the drug therapy. Image-guided placement of the tip of a drug delivery catheter directly into specific regions of the brain can initially produce maximal drug concentration close to some targeted loci of tissue receptors following delivery of the drug. At the same time, the limited distribution of drug injected from a single catheter tip presents other problems. For example, the volume flow rate of drug delivery must be very low to avoid indiscriminate hydrodynamic damage or other damage to brain cells and nerve fibers. Delivery of a drug from a single point source may also limit the distribution of the drug by decreasing the effective radius of penetration of the drug agent into the surrounding tissue receptor population. Positive pressure infusion, i.e., convection-enhanced delivery of drugs into the brain, as taught by U.S. Pat. No. 5,720,720 may overcome the problem of effective radius of penetration. Also, U.S. patent application Ser, No. 08/857,043, filed on May 15, 1997 and titled “Method and Apparatus for Use with MR Imaging” describes a technology comprising a method for observing the delivery of material to tissue in a living patient comprising the steps of a) observing by magnetic resonance imaging a visible image within an area or volume comprising tissue of said living patient, the area or volume including a material delivery device, b) delivering at least some material by the material delivery device into the area or volume comprising tissue of a living patient, and c) observing a change in property of said visible image of the area or volume comprising tissue of a living patient while said material delivery device is still present within the area or volume. This process, including the MRI visualization, is performed in approximately or actually real time, with the clinical procedure being guided by the MRI visualization.
U.S. Pat. Nos. 4,869,247, 5,654,864, 5,125,888, 5,707,335 and 5,779,694 describe processes and apparatus for the use of magnetic stereotaxis for the manipulation of an object or implant which is moved into position within a patient, particularly within the cranial region and specifically within the brain but in principle elsewhere in the body also.
Research on magnetic catheterization of cerebral blood vessels generally has focused on design of transvascular devices to thrombose aneurysms, to deliver cytotaxic drugs to tumors, and to deliver other therapies without the risks of major invasive surgery. Examples of such studies include Hilal et al (J. Appl. Phys. 40:1046, 1969), Molcho et al (IEEE Trans. Biomed. Eng. BME 17, 134, 1970), Penn et al (J. Neurosurg. 38:239, 1973), and Hilal et al (Radiology 113:529,1974). U.S. Pat. Nos. 4,869,247, 5,654,864, 5,125,888, 5,707,335 and 5,779,694 describe processes and apparatus for the use of magnetic stereotaxis for the manipulation of an object or implant which is moved into position within a patient, particularly within the cranial region and specifically within the brain but in principle elsewhere in the body also. These patents do no not involve any contemplation of real time visualization of drug distribution within the brain, especially by MRI. It should be noted that the potential exists for interactive interference between the two systems, magnetic resonance imaging and magnetic stereotaxis, particularly where fine images are being provided by a system based on magnetic coils, especially as described in U.S. patent application Ser. No. 08/916,596, filed on Aug. 22, 1997, which is incorporated herein by reference for its disclosure of the design, construction, structure and operation of coils and catheters in MR-guided procedures.
One recently established method of reading the data obtained from the MR imaging is technically founded upon existing knowledge of Apparent Diffusion Coefficients (ADC) in particular regions of the body. There is significant published literature with respect to ADC values for specific tissues in various parts of animals, including various tissues of humans (e.g., Joseph V. Hajnal, Mark Doran, et al., “MR Imaging of Anisotropically Restricted Diffusion of Water in the Nervous System: Technical, Anatomic, and Pathological Considerations,” Journal of Computer Assisted Tomography, 15(1): 1-18, January/February, 1991, pp. 1-18). It is also well established in the literature that loss of tissue structure through disease results in a decrease of the ADC, as the tissue becomes more like a homogeneous suspension. Clinical observations of changes in diffusion behavior have been made in various tissue cancers, multiple sclerosis, in strokes (where the reduction in diffusion precedes the increase in T2), and in epilepsy. (e.g., Y. Hasegawa, L. Latour, et al. “Temperature Dependent Change of Apparent Diffusion Coefficient of Water in Normal Ischemic Brain”, Journal of Cerebral Blood Flow and Metabolism 14:389-390, 1994).Thus, ADC values are specific for specific types of tissues. Accordingly, as different drugs/chemicals are introduced into a tissue volume under MR observation, the change in ADC resulting from each drug/chemical interaction with the ambient water proton environment can be observed.
While the ADC is the preferred means within the present invention of mapping the delivery of drug in tissue, other embodiments of the invention allow for additional tissue contrast parameters to track the delivery of a drug into tissue. In other words, the delivery of a drug into tissue will cause other MRI-observable changes which can be mapped (as is done for ADC) and which can be used to map the spatial distribution characteristics of the drug within and around the targeted tissue. While some of these observations may be larger in magnitude than others, any of the MRI contrast mechanisms' effects can be used as a tracking mechanism to longitudinally evaluate the spatial kinetics of drug movement within the imaging volume.
The tissue contrast changes apparent on an MR image can arise from ADC, from alterations in the BO magnetic field (often referred to as magnetic susceptibility or ABO produced by the presence of a substance in said tissue), from alterations in local tissue T1 relaxation times, from local T2 relaxation times, from T2* relaxation times (which can be created by susceptibility differences), from the magnetization transfer coefficients (MTC is an effect produced by local communication between free water protons and those of nearby macromolecular structures), from the ADC anisotropy observed in oriented matter, and also from local differences in temperature which will affect in varying degrees all of the included tissue contrast parameters. In addition, the delivery of drug can also be tracked from magnetic field frequency shifts caused by the drug or arising from agents (e.g., MR taggants) added with unique frequency shifts from those of the local protons (such as that created from F-19 or fluorine-19 agents found in or added to the drug).
MR imaging of the alterations in the BO magnetic field (also known as imaging of the local magnetic susceptibility) can reveal the spatial distribution of a drug from the interaction of the drug with the otherwise homogeneous magnetic field found in MRI. To enhance the alterations in the magnetic field BO caused by the drug, small amounts of a BO-altering added agent or agents can be added to the drug during delivery. This can include iron oxide particles, or other materials, such as those comprising lanthanide-, manganese-, and iron-chelates. In addition, vehicles containing differing gases (N2, O2, CO2) will also alter the local magnetic field and thus produce a magnetic susceptibility effect which can be imaged.
Targeted delivery of drug agents may be performed by any therapeutically effective drug delivery device or system, including, for example, those utilizing MR-compatible pumps connected to variable-length concentric MR-visible dialysis probes each with a variable molecular weight cut-off membrane, or by another MR-compatible infusion device which injects or infuses a diagnostic or therapeutic drug solution. Imaging of the injected or infused drug agent is performed by MR diffusion mapping using the RF microcoils attached to the distal shaft of the injection device, or by imaging an MR-visible contrast agent that is injected or infused through the walls of the dialysis fiber into the brain. The delivery and distribution kinetics of injections or infusions of drug agents at rates, for example, of between 1 ml/min (or less) to 1000 ml/min (or more) are monitored quantitatively and non-invasively using real-time contrast-enhanced magnetic susceptibility MR imaging combined with water proton directional diffusion MR imaging.
Non-invasive examination procedures for the mammaries have proven to be of significant early diagnostic benefit. However, there is significant pain and discomfort involved in the present procedures that causes many patients to resist regular and early examination. MRI guided interventional procedures for mammary examinations require their own unique procedures to be acceptable to the patients.